Rationally Engineered AAV Capsids Improve Transduction and Volumetric Spread in the CNS.

ABSTRACT: Adeno-associated virus (AAV) is the most common vector for clinical gene therapy of the CNS. This popularity originates from a high safety record and the longevity of transgene expression in neurons. Nevertheless, clinical efficacy for CNS indications is lacking, and one reason for this is the relatively limited spread and transduction efficacy in large regions of the human brain. Using rationally designed modifications of the capsid, novel AAV capsids have been generated that improve intracellular processing and result in increased transgene expression. Here, we sought to improve AAV-mediated neuronal transduction to minimize the existing limitations of CNS gene therapy. We investigated the efficacy of CNS transduction using a variety of tyrosine and threonine capsid mutants based on AAV2

SUBMITTER: Kanaan NM 

PROVIDER: S-EPMC5503098 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature